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Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus (PALACE)

Primary Purpose

Esophageal Squamous Cell Carcinoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Pembrolizumab

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring esophageal squamous cell carcinoma, neoadjuvant chemoradiotherapy, pembrolizumab, immune therapy, checkpoint inhibitor

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

A patient will be eligible for inclusion in this study only if ALL of the following criteria apply:
1. Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell carcinoma
2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
3. Patients approve and sign the informed consent

Exclusion Criteria:

1. Patients with active autoimmune disease or history of autoimmune disease 2. Patients who have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications 3. Subjects with a history of symptomatic interstitial lung disease 4. History of allergy to study drug components 5. Women must not be pregnant or breast-feeding 6. Men with female partners (WOCBP) that are not willing to use contraception 7. Patient has received prior chemotherapy, radiotherapy, target therapy and immune therapy for this malignancy or for any other past malignancy 8. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events

Sites / Locations

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

Arm 1:preoperative pembrolizumab with chemoradiotherapy group Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 15 and 29. Surgery will be performed within 6 weeks after completion of preoperative therapy described above.

Outcomes

Primary Outcome Measures

Safety(The rates of grade 3 and higher-grade treatment-related adverse events)

Incidence of adverse events using CTCAE 4.03;grade 3 treatment-related adverse events and higher-grade adverse event will be reported

Secondary Outcome Measures

Feasibility (The rates of patients who finished pembrolizumab with chemoradiotherapy and receive surgery within 6 weeks after preoperative therapies.)

Feasibility was defined as completion of surgery within 6 weeks after preoperative therapies.

Pathologic complete response

Pathologic complete response was defined as pT0N0M0

Radiographic response

To assess radiographic response to neoadjuvant pembrolizumab with concurrent chemoradiotherapy using RECIST 1.1.

Full Information

NCT ID

NCT03792347

First Posted

December 28, 2018

Last Updated

May 31, 2020

Sponsor

Hecheng Li M.D., Ph.D

1. Study Identification

Unique Protocol Identification Number

NCT03792347

Brief Title

Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus

Acronym

PALACE

Official Title

A Phase Ib Study of Pre-Operative Pembrolizumab + Chemoradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Unknown status

Study Start Date

January 21, 2019 (Actual)

Primary Completion Date

March 17, 2020 (Actual)

Study Completion Date

June 17, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Hecheng Li M.D., Ph.D

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer treatment.

Detailed Description

Esophageal cancer ranks the eighth most common cancer (the fifth most common cancer in China), while ESCC is the most common subtype in Asia (more than 90 % in china). Radical resection is thought to be the mainstay of esophageal cancer treatment and preoperative CRT is well applied in treating locally advanced esophageal cancer. In a multicohort, phase IB study, pembrolizumab was used in 23 unresectable esophageal cancer patients. In this clinical trial, the incidence of grade 3 treatment-related adverse events was 39 % without the appearance of grade 4 and higher-grade adverse event, while the overall response rate reached 30 %. The safety of immune checkpoint therapy for unresected esophageal cancers using nivolumab, a different PD-1 monoclonal antibody, has also been confirmed by high quality clinical trials. This study will evaluate the safety and feasibility of preoperative immune checkpoint therapy using pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma. And this study will provide valuable information for further clinical trials of preoperative pembrolizumab and other immune checkpoint therapy in esophageal cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Squamous Cell Carcinoma

Keywords

esophageal squamous cell carcinoma, neoadjuvant chemoradiotherapy, pembrolizumab, immune therapy, checkpoint inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 1 and 22. Surgery will be performed within 6 weeks after completion of preoperative therapy described above

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

Keytruda

Intervention Description

Arm1：Pre-operative Pembrolizumab+chemoradiotherapy

Primary Outcome Measure Information:

Title

Safety(The rates of grade 3 and higher-grade treatment-related adverse events)

Description

Incidence of adverse events using CTCAE 4.03;grade 3 treatment-related adverse events and higher-grade adverse event will be reported

Time Frame

From date of treatment allocation until surgery was applied during study period or up to at least 90 days after last dose

Secondary Outcome Measure Information:

Title

Feasibility (The rates of patients who finished pembrolizumab with chemoradiotherapy and receive surgery within 6 weeks after preoperative therapies.)

Description

Feasibility was defined as completion of surgery within 6 weeks after preoperative therapies.

Time Frame

From date of treatment allocation until surgery or definitive chemoradiotherapy was applied,whichever came first, assessed up to 5 months

Title

Pathologic complete response

Description

Pathologic complete response was defined as pT0N0M0

Time Frame

From date of treatment allocation and during treatment period up to 1 year

Title

Radiographic response

Description

To assess radiographic response to neoadjuvant pembrolizumab with concurrent chemoradiotherapy using RECIST 1.1.

Time Frame

From date of treatment allocation and during treatment period up to 3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: A patient will be eligible for inclusion in this study only if ALL of the following criteria apply: Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell carcinoma Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Patients approve and sign the informed consent Exclusion Criteria: 1. Patients with active autoimmune disease or history of autoimmune disease 2. Patients who have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications 3. Subjects with a history of symptomatic interstitial lung disease 4. History of allergy to study drug components 5. Women must not be pregnant or breast-feeding 6. Men with female partners (WOCBP) that are not willing to use contraception 7. Patient has received prior chemotherapy, radiotherapy, target therapy and immune therapy for this malignancy or for any other past malignancy 8. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hecheng Li, MD PHD

Organizational Affiliation

Ruijin Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ruijin Hospital, Shanghai JiaoTong University School of Medicine

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200025

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

33373868

Citation

Li C, Zhao S, Zheng Y, Han Y, Chen X, Cheng Z, Wu Y, Feng X, Qi W, Chen K, Xiang J, Li J, Lerut T, Li H. Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1). Eur J Cancer. 2021 Feb;144:232-241. doi: 10.1016/j.ejca.2020.11.039. Epub 2020 Dec 26.

Results Reference

derived

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Preoperative Anti-PD-1 Antibody Combined With Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus

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